Leukocytes are required for the trypsin-induced increase in lung vascular permeability

The authors examined the role of leukocytes in mediating the increase in lung vascular permeability induced by trypsin infusion in the sheep lung lymph preparation. One group of sheep was challenged with an intravenous infusion of trypsin (4.5 mg/kg/hr). A second group was depleted of 80% of circulating granulocytes and of 48% of circulating lymphocytes by repeated injections of hydroxyurea several days prior to the trypsin infusion. Pulmonary lymph flow and transvascular protein clearance increased twofold without changes in pulmonary vascular pressures in the control group, suggesting that trypsin resulted in an increase in pulmonary vascular permeability. The hydroxyurea-induced leukopenia prevented the increases in pulmonary lymph flow and protein clearance after the trypsin infusion, indicating that leukocytes are required for increase in lung vascular permeability. Because neutrophil activation may mediate the trypsin-induced increase in lung vascular permeability, we assessed the effect of trypsin on superoxide anion (O2-) generation by isolated neutrophils. Trypsin (0.09 mg/ml) added to isolated sheep neutrophils did not increase O2- generation more than neutrophils in buffer. The supernatant obtained after incubation of trypsin with citrated whole blood increased O2- generation from isolated neutrophils, this response was greater than with trypsin alone. Therefore, neutrophil activation occurs as a result of the action of trypsin on whole blood. Neutrophil activation may contribute to the leukocyte-dependent increase in lung vascular permeability after trypsin.